The risk of birth defects in offspring of diabetic women is increased four- to nine-fold. The mechanism by which diabetes affects maldevelopment is not entirely clear, but experimental evidence suggests a direct role of hyperglycemia. Intakes of high glycemic load diets are associated with type 2 diabetes, as well as other cardiovascular outcomes. We hypothesize that hyperglycemia, as measured by average dietary glycemic load and glycemic index, during the periconceptional period, increases the risk of birth defects in non- diabetic women. Several studies have also shown that overweight and obese women have 1.7- to 3-fold increased risks of neural tube defects and other birth defects, which are independent from the risk associated with diabetes. We further hypothesize that the effects of high glycemic diet on birth defect risks are exacerbated in overweight and obese women due to insulin resistance and are ameliorated by antioxidant supplementation. These hypotheses will be addressed using data from two case-control studies - the Slone Epidemiology Center Birth Defects Study (1988 to 2005) and the National Birth Defects Prevention Study (1998 to 2005). Each study identifies cases with major malformations and nonmalformed controls. Mothers of cases and controls are interviewed about pregnancy events and exposures, including periconceptional dietary intake measured by long and short versions of the Willett food frequency questionnaire. Dietary data will be available on over 24,000 cases with birth defects and over 10,000 non- malformed controls. Average glycemic index will be calculated by summing the product of glycemic index and frequency of servings across all food items. Glycemic load will be calculated by summing the product of glycemic index, frequency of servings, and carbohydrate content across all food items. Glycemic index values were collected from literature and Medline reviews or from direct measurement. Overall birth defect risks and specific birth defect risks will be estimated for average glycemic load and glycemic index after adjusting for total caloric intake, study center, year of infant's birth, maternal age and education, cigarette smoking, and folic acid intake. Interactions between glycemic intake, BMI, and antioxidant supplementation will also be examined for birth defects overall and the following specific birth defect groups: neural tube (n approximately 1000), cardiovascular (n approximately 9800), musculoskeletal (n approximately 3300), gastrointestinal (n approximately 2700), and urinary tract (n approximately 1700). [unreadable] [unreadable] [unreadable]